Longitudinal biobanks-based study on the joint effects of infections, nutrition and hormones on risk of prostate cancer.

Background To evaluate the individual and combined effects of enterolactone, vitamin D, free testosterone, Chlamydia trachomatis and HPV-18 on the risk of prostate cancer in a large population-based biochemical material that combined three Nordic serum sample banks. Material and methods A joint cohort of 209 000 healthy men was followed using cancer registry linkages. From this cohort altogether 699 incident cases of prostate cancer were identified. Four controls were selected by incidence density sampling and matching for country, age and date of the blood sampling. Complete data for all investigated exposures was available for 483 eligible cases and 1055 eligible controls. Multivariate regression analyses were performed to investigate the solitary and combined effects. Results The solitary effects were small. Significantly increased risk [rate ratio 1.6 (95% CI 1.0-2.5)] was found in those seronegative for C. trachomatis infection. The joint effect in risk levels of enterolactone and vitamin D was antagonistic [observed rate ratio (RR) 1.4 (1.0-2.1), expected RR 2.0 (1.0-4.1)] as well as that of HPV-18 and C. trachomatis [observed RR 1.9 (0.8-4.5), expected RR 9.9 (1.1-87.0)]. Conclusion A large follow-up study combining data from several previously investigated exposures to investigate joint effects found no evidence that exposure to two risk factors would increase the risk of prostate cancer from that expected on basis of exposure to one risk factor. If anything, the results were consistent with antagonistic interactions.

Dual role of physical workload and occupational noise in the association of the metabolic syndrome with risk of coronary heart disease: findings from the Helsinki Heart Study.

OBJECTIVES: Previous evidence indicates that occupational exposure to physical workload or noise entails development of hypertension and risk of coronary heart disease (CHD). However, vigorous physical activity lessens the risks of the metabolic syndrome (MetS) and CHD. We explored this issue by studying the joint effect of physical workload or noise and MetS on risk of CHD. METHODS: This 18-year follow-up study comprised 1502 middle-aged men employed in industry who participated in the second screening for the Helsinki Heart Study but were not treated with gemfibrozil, the trial drug. The CHD endpoints (ICD-9 codes 410-414 and ICD-10 codes 120-125) were obtained from official Finnish registers. The Finnish job-exposure matrix FINJEM provided information on occupational exposures. The joint effect of baseline MetS levels and both occupational exposures was estimated using Cox's regression models. RESULTS: Workload and noise increased CHD risk due to increased blood pressure, glucose or body mass index (BMI), separately or combined: the joint effect of workload and MetS defined using these three components yielded an RR of 5.21 (95% CI 2.70 to 10.05). However, when MetS was defined using elevated BMI, high triglycerides and low high-density lipoprotein cholesterol, an RR of 2.19 (95% CI 1.11 to 4.30) among those with MetS only reduced to 1.20 (95% CI 0.61 to 2.35) if concurrently exposed to workload. CONCLUSIONS: Occupational exposure to workload or noise modifies CHD risk differently depending on which definition of MetS is used. In the presence of physical workload or noise, hypertension and blood glucose were the best predictors.

Joint effect of self-reported sleep problems and three components of the metabolic syndrome on risk of coronary heart disease.

OBJECTIVE: This study explored the joint effect of two epidemics, sleep problems and metabolic syndrome (MetS), on the risk of coronary heart disease (CHD). METHODS: The study group is part of the Finnish middle-aged men who participated in the first screening for the Helsinki Heart Study (HHS) in 1981-1982. At that time, three components of MetS were measured: body mass index, HDL cholesterol, and blood pressure. Later, in 1986-1988, they were given a psychosocial questionnaire including items on sleep problems. Of the respondents, 2753 formed our study group and were followed up using population-based registers until 1995. The relative risks (RR) of CHD were estimated using Cox's regression models. RESULTS: When several sleep problems were present simultaneously, some increased CHD risk was observed. However, when considered jointly with MetS, insomnia or daytime fatigue approximately doubled the CHD risk and the presence of insufficient sleep more than tripled the risk. Among those who had MetS only, the RR was 2.55, and among those with both insufficient sleep and MetS the RR was 9.36 (95% confidence interval: 4.60-19.04; P for interaction 0.09) when compared to those with no insufficient sleep and no components of MetS. CONCLUSION: The interaction occurred when all three measured MetS components were present, suggesting that co-occurrence of these two epidemics may predict growing public health problems.

Estimation of VLDL, IDL, LDL, HDL2, apoA-I, and apoB from the Friedewald inputs--apoB and IDL, but not LDL, are associated with mortality in type 1 diabetes.

BACKGROUND: There is an unmet need for a straightforward and cost-effective assessment of multiple lipoprotein risk factors for vascular diseases. AIMS: 1) To study the relation of various lipoprotein lipid and apolipoprotein (apo) measures on the Friedewald inputs, i.e. plasma triglycerides (TG), cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C). 2) To build up regression models for the appropriate measures based solely on the Friedewald inputs. METHODS: Data were available for 1,775 plasma samples, from which very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and HDL were also isolated by ultracentrifugation. For HDL(2)-C and apolipoproteins, 343 and 247 samples were available, respectively. RESULTS: Accurate models were obtained for VLDL-TG (cross-validation r=0.98), LDL-C (r=0.91), HDL(2)-C (r=0.92), apoA-I (r=0.92), and apoB (r=0.95). A semi-quantitative model was obtained for IDL-C (r=0.78). Due to the anticipated role of IDL-C in atherosclerosis, it was still kept within the accepted models and pursued further. The associations of the estimates with premature deaths were studied in 4,084 patients with type 1 diabetes. The associations of IDL-C and LDL-C were markedly different, the best predictors of mortality being apoB, apoB to apoA-I ratio, and IDL-C. CONCLUSIONS: The new models allow identification of clinically relevant lipoprotein profiles with no added cost to the conventional Friedewald formula.

Nordic biological specimen banks as basis for studies of cancer causes and control--more than 2 million sample donors, 25 million person years and 100,000 prospective cancers.

The Nordic countries have a long tradition of large-scale biobanking and comprehensive, population-based health data registries linkable on unique personal identifiers, enabling follow-up studies spanning many decades. Joint Nordic biobank-based studies provide unique opportunities for longitudinal molecular epidemiological research. The purpose of the present paper is to describe the possibilities for such joint studies, by describing some of the major Nordic biobank cohorts with a standardised calculation of the cancer incidence in these cohorts. Altogether two million donors have since 1966 donated more than four million biological samples, stored at -20 degrees C to -135 degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a result of joint database handling principles, the accuracy of personal identifiers and completeness of follow-up for vital status in all participating biobanks was improved. Thereafter, the cancer incidence was determined using follow-up through the national cancer registries. Biobanks based on random samples of population typically showed slightly lower cancer incidence rates than the general population, presumably due to better participation rates among health-conscious subjects. On the other hand, biobanks including samples for viral screening or clinical testing showed 1.5 to 2.1 fold increased incidence of cancer. This excess was very high immediately after sampling, but for some cancer sites remained elevated for years after clinical sampling. So far, more than 100 000 malignant neoplasms have occurred after sample donation, and the annual increase of the cancer cases in these cohorts is about 10 000. The estimates on the population-representativity of the biobanks will assist in interpretation of generalizability of results of future studies based on these samples, and the systematic tabulations of numbers of cancer cases will serve in study power estimations. The present paper summarizes optimal study designs of biobank-based studies of cancer.

Interaction of factors related to the metabolic syndrome and vitamin D on risk of prostate cancer.

BACKGROUND: Factors related to the metabolic syndrome and low levels of vitamin D have been implicated as risk factors for prostate cancer. Insofar, no studies have assessed their joint effects on prostate cancer risk. METHODS: We studied (a) the associations of vitamin D with the metabolic syndrome factors body mass index, systolic and diastolic blood pressure, and high-density lipoprotein cholesterol (HDL-C) and (b) the prostate cancer risk associated with these factors and especially their joint effects with vitamin D on risk of prostate cancer. We did a longitudinal nested case-control study on 132 prostate cancer cases and 456 matched controls from a cohort of 18,939 Finnish middle-aged men from the Helsinki Heart Study. The odds ratios (OR) of prostate cancer were assessed via conditional logistic regression analysis. RESULTS: Apart from HDL-C, there was no linear association between the metabolic syndrome factors and vitamin D levels. In univariate analysis, men in the highest quartiles of body mass index (>28 kg/m(2)) and systolic blood pressure (>150 mmHg) showed a modest increase in risks of prostate cancer, with ORs of 1.37 (P = 0.16) and 1.53 (P = 0.05) when compared with the three lower quartiles, but low HDL-C entailed no prostate cancer risk. However, with all three factors present, the OR was 3.36 (P = 0.02), and jointly with low vitamin D (

Shift work, occupational noise and physical workload with ensuing development of blood pressure and their joint effect on the risk of coronary heart disease.

OBJECTIVES: The change in systolic blood pressure (SBP) over an 8-year period was explored in groups defined according to exposure to shift work, occupational noise, and physical workload. The impact of baseline SBP and its increase in relation to coronary heart disease (CHD) risk due to these exposures was also studied. METHODS: The study cohorts (N=1288 for CHD follow-up, N=884 for SBP follow-up) consisted of industrially employed middle-aged men from the Helsinki Heart Study. Shiftwork status was obtained from a questionnaire, and other exposures were determined with the Finnish job-exposure matrix. SBP was measured in the Helsinki Heart Study, and CHD end points were obtained from official Finnish registers. The joint effects of baseline SBP, its change, and the exposure in question were estimated via Cox s regression models. RESULTS: During the SBP follow-up, the steepest SBP gradient was found for physical workload only and physical workload combined with noise; shift work alone or combined with noise primarily entailed a lower mean SBP level than no such exposure. However, the shift workers had a relative risk of 1.71 [95% confidence interval (95% CI) 1.01-2.87] even without an increase in SBP, but, with a baseline SBP of > or = 140 mmHg and an additional increase, their relative risk rose to 4.62 (95% CI 2.31-9.24) when they were compared with day workers with an SBP of <140 mmHg and no increase. CONCLUSIONS: In general, shift workers do not develop higher SBP levels than day workers, but, if they do, it entails high CHD risk. Noise shows a similar pattern. In contrast, physical workload entails a significant increase in SBP, and SBP is a key pathway to CHD risk.

The sense of coherence and incidence of cancer--role of follow-up time and age at baseline.

OBJECTIVE: We studied the effect of the sense of coherence (SOC) on cancer incidence, the role of age at baseline, and the length of the follow-up in that association. METHODS: Five thousand eight hundred sixty-six middle-aged men initially in working life were followed up for 12 years after measurement of the SOC. The relative risks (RRs) of cancer were estimated using Cox regression models. RESULTS: For all cancers combined in 8-year follow-up, those with a weak SOC had a higher RR of cancer 1.52 [95% confidence interval (CI), 1.12-2.06] than those with a strong SOC. However, the effect weakened in 12-year follow-up (RR 1.14; 95% CI 0.93-1.42). The greatest risk was seen in a subcohort consisting of those aged >or=55 years at baseline with a weak SOC: the RR was 1.65 (1.12-2.43) in 8-year follow-up and 1.40 (1.05-1.85) in 12-year follow-up. CONCLUSION: A strong SOC seemed to delay the onset of cancer more clearly among men over 55 years of age.

Chlamydia pneumoniae antibody levels before coronary events in the Helsinki Heart Study as measured by different methods.

The lack of specific tests for the diagnosis of chronic Chlamydia pneumoniae infection has led to the use of enzyme immunoassay (EIA) instead of the gold standard, that is, microimmunofluorescence (MIF), in the measurement of C. pneumoniae antibodies. We assessed the predictive values of C. pneumoniae antibody levels and seroconversions measured by MIF and EIA for coronary events in the prospective Helsinki Heart Study. Sera from 239 cases with coronary events and 239 controls were available at the baseline and data from 210 cases and 211 controls before and after the event. The agreement between MIF and EIA antibody levels was best in high antibody titers. In conditional logistic regression analysis, only high IgA MIF titers (>/=40) at the baseline predicted future coronary events, and the participants with MIF seroconversion between consecutive sera had a higher (nonsignificant) risk for coronary events than the controls. The difference in the kinetics of EIA and MIF antibodies demonstrated that MIF should remain the gold standard.

Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of the Helsinki Heart Study.

BACKGROUND: The Helsinki Heart Study was a double-blind, placebo-controlled primary prevention trial among 4081 dyslipidemic middle-aged men to test the efficacy of gemfibrozil in the prevention of coronary heart disease (CHD). After the 5-year trial, the participants were notified of their treatment group and invited to continue or start gemfibrozil therapy free of charge through 1995. Approximately two thirds of participants in both groups chose gemfibrozil therapy. In this 18-year follow-up through 2000, we compared the CHD, cancer, and all-cause mortality among subjects in the original gemfibrozil (OG) group (n = 2046) with those in the original placebo (OP) group (n = 2035). METHODS: To provide an overview of the absolute risks in the 2 treatment groups as well as risk differences between them, we calculated crude mortality rates and presented Kaplan-Meier plots of survival with log-rank tests. We also estimated the relative risks (RRs) using Cox proportional hazards models with and without covariates. RESULTS: During the follow-up until 1995, subjects in the OG group had a 32% lower RR of CHD mortality (P = .03) compared with those in the OP group, and when followed up until 2000, the RR was 23% lower (P = .05). Overall, there were no differences in all-cause or cancer mortality. However, those in the OG group with both body mass index and triglyceride level in the highest tertiles had a 71% lower RR of CHD mortality (P<.001), a 33% lower RR of all-cause mortality (P = .03), and a 36% lower RR of cancer mortality (P = .22) compared with those in the OP group. CONCLUSION: Long-term mortality follow-up showed that patients with dyslipidemia benefited from beginning treatment with gemfibrozil early, especially if their dyslipidemia entailed factors related to the metabolic syndrome.

Long-term effect of occupational noise on the risk of coronary heart disease.

OBJECTIVES: The aim of the study was to investigate the short- and long-term effects of occupational exposure to continuous and impulse noise on the risk of CHD. METHODS: The effect of noise on CHD was studied among 6005 Finnish middle-aged industrially employed men (part of the screeners in the Helsinki Heart Study) in a prospective 18-year follow-up study. The CHD end points (codes 410-414 in the ninth revision of the International Classification of Diseases and codes I20-I25 in the tenth revision) were obtained from official Finnish registers. The Finnish job-exposure matrix FINJEM provided estimates of the proportion of exposed persons and the mean level of exposure among those exposed by occupation. The relative risks (RR) of CHD and the 95% confidence intervals (95% CI) for noise exposure were calculated from Cox's proportional hazard models with adjustment for some other risk factors of CHD. RESULTS: The short-term (9-year follow-up) relative risk of CHD for the combined noise (continuous noise exceeding 80 decibels and impulse noise) was 1.38 (95% CI 1.04-1.82), and the long-term (18-year follow-up) RR was 1.54 (95% CI 1.28-1.86). For blue-collar workers the corresponding estimates were 1.11 (95% CI 0.82-1.51) and 1.29 (95% CI 1.05-1.57). Adjustment for other relevant risk factors did not materially change the results. CONCLUSIONS: In our long-term follow-up of industrially employed men, exposure to noise, especially to impulse noise, was associated with a moderate, but statistically significant increase in CHD risk that persisted even after the workers had passed the age of retirement.

Chlamydial antibodies and risk of prostate cancer.

OBJECTIVE: We assessed the risk of prostate cancer by exposure to Chlamydia trachomatis. METHOD: Seven hundred thirty eight cases of prostate cancer and 2,271 matched controls were identified from three serum sample banks in Finland, Norway, and Sweden by linkage to the population based cancer registries. RESULTS: A statistically significant inverse association (odds ratio, 0.69; 95% confidence interval, 0.51-0.94) was found. It was consistent by different serotypes and there was a consistent dose-response relationship. CONCLUSION: C. trachomatis infection is not likely to increase the risk of prostate cancer. Whether the inverse relationship is true or due to difficulties in measuring the true exposure in prostatic tissue by serology, confounders or other sources of error remain open.

Serum iron, infection and inflammation; effects on coronary risk.

OBJECTIVES: To explore the potential pathways of association between serum iron and coronary heart disease, with major emphasis on factors related to infections and inflammation. DESIGN: A nested case-control study with 215 cases (myocardial infarction or coronary death) and 215 matched controls over 8.5 years. Logistic regression analyses were used to compare relative risks in various serum iron-high sensitive CRP-total leucocyte count-herpes simplex virus-1 antibody categories. RESULTS: Participants with low iron (< 17 micromol/l) had increased coronary risk with Odds Ratio (OR) of 2.1 (95% CI 1.1-3.8). Simultaneous elevation of hs-CRP and leucocyte count increased the risk substantially in those with low iron, OR 9.8 (95% CI 3.9-24.4). A combination of high herpes simplex virus-1 antibody level and low iron increased the risk modestly (OR 1.2), but when hs-CRP level was high simultaneously, the OR was 13.1 (95% CI 2.9-60.1). CONCLUSIONS: Our data suggest an association between low serum iron level and coronary risk. The association is not independent, but is related to the fact that chronic infections and inflammation are accompanied with low serum iron.

High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study.

Androgens stimulate prostate cancer in vitro and in vivo. However, evidence from epidemiologic studies of an association between circulating levels of androgens and prostate cancer risk has been inconsistent. We investigated the association of serum levels of testosterone, the principal androgen in circulation, and sex hormone-binding globulin (SHBG) with risk in a case-control study nested in cohorts in Finland, Norway and Sweden of 708 men who were diagnosed with prostate cancer after blood collection and among 2,242 men who were not. In conditional logistic regression analyses, modest but significant decreases in risk were seen for increasing levels of total testosterone down to odds ratio for top vs. bottom quintile of 0.80 (95% CI = 0.59-1.06; p(trend) = 0.05); for SHBG, the corresponding odds ratio was 0.76 (95% CI = 0.57-1.01; p(trend) = 0.07). For free testosterone, calculated from total testosterone and SHBG, a bell-shaped risk pattern was seen with a decrease in odds ratio for top vs. bottom quintile of 0.82 (95% CI = 0.60-1.14; p(trend) = 0.44). No support was found for the hypothesis that high levels of circulating androgens within a physiologic range stimulate development and growth of prostate cancer.

Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries.

Vitamin D inhibits the development and growth of prostate cancer cells. Epidemiologic results on serum vitamin D levels and prostate cancer risk have, however, been inconsistent. We conducted a longitudinal nested case-control study on Nordic men (Norway, Finland and Sweden) using serum banks of 200,000 samples. We studied serum 25(OH)-vitamin D levels of 622 prostate cancer cases and 1,451 matched controls and found that both low (/=80 nmol/l) 25(OH)-vitamin D serum concentrations are associated with higher prostate cancer risk. The normal average serum concentration of 25(OH)-vitamin D (40-60 nmol/l) comprises the lowest risk of prostate cancer. The U-shaped risk of prostate cancer might be due to similar 1,25-dihydroxyvitamin D(3) availability within the prostate: low vitamin D serum concentration apparently leads to a low tissue concentration and to weakened mitotic control of target cells, whereas a high vitamin D level might lead to vitamin D resistance through increased inactivation by enhanced expression of 24-hydroxylase. It is recommended that vitamin D deficiency be supplemented, but too high vitamin D serum level might also enhance cancer development.

Synergistic effect of persistent Chlamydia pneumoniae infection, autoimmunity, and inflammation on coronary risk.

BACKGROUND: Given the role of chronic infections, autoimmunity, and inflammation in atherosclerosis, we studied the joint effect of chronic Chlamydia pneumoniae infection, persistently elevated human heat-shock protein 60 (hHsp60) antibodies, and C-reactive protein (CRP) on coronary risk. METHODS AND RESULTS: The participants for this prospective nested case-control study were obtained from the Helsinki Heart Study, during which 241 nonfatal myocardial infarctions or coronary deaths occurred among 4081 dyslipidemic middle-aged men. Serum samples taken at baseline and 3 to 6 months before the coronary events that occurred during the 8.5-year period were analyzed for antibodies to C pneumoniae and hHsp60 and the CRP concentration. Compared with persistently low levels, the risk of coronary events was 2-fold for persistently elevated immunocomplex (IC)-bound and/or serum IgA antibodies to C pneumoniae (OR, 1.96; 95% CI, 1.14 to 3.36) and also for serum IgA antibodies to hHsp60 (OR, 2.11; 95% CI, 1.08 to 4.13). The risks associated with elevated antibodies were much higher when CRP was also elevated. Compared with low or transiently elevated levels, the risk of coronary events, with adjustment for age and smoking, was 4.5-fold for persistently elevated CRP and C pneumoniae IC/IgA antibodies together (OR, 4.47; 95% CI, 1.84 to 10.83) and was similar for CRP and hHsp60 IgA antibodies together (OR, 4.36; 95% CI, 1.53 to 12.39). CONCLUSIONS: Persistently but not transiently elevated C pneumoniae IC/IgA and hHsp60 IgA antibodies, especially when present together with an elevated CRP level, predicted coronary events.

Insulin sensitivity markers: predictors of accidents and suicides in Helsinki Heart Study screenees.

The purpose of this study was to evaluate whether elements signifying relative insulin sensitivity (IS) were prospectively linked to accidents and suicides in 14,976 Helsinki Heart Study (HHS) screenees. The main outcome measure was hospitalizations and deaths from accidents and suicide attempts determined from Finnish registries, in aggregate; and separating out suicides (and attempts). Cox proportional hazards regression was used to determine adjusted risk ratios (RR) relating IS characteristics (extreme quartiles of high HDL-C, low BMI, and low SBP), individually and conjointly, to subsequent accidents or suicides (including attempts), adjusted for age, alcohol use, smoking, and non-HDL cholesterol. Each IS element was related to combined hospitalization and death, from accidents and from suicide attempts; increasing numbers of these characteristics were associated with increased risk, an effect that was more powerful and statistically significant for suicide. For accidents, the presence of one and two to three IS characteristics provided RRs (95% confidence intervals (CI)) of 1.08 (0.97-1.20) and 1.14 (0.98-1.31), respectively. For suicides including attempts, RRs (95%CI) were 1.61 (1.09-2.38) for one IS factor, and 1.88 (1.18-2.98) for two to three IS factors, while for completed suicides, the figures were 2.01 (1.19-3.38) and 2.24 (1.20-4.17), respectively. We speculate that insulin sensitivity may relate to these outcomes through low central serotonin activity.

Circulating enterolactone and prostate cancer risk: a Nordic nested case-control study.

Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by the intestinal microflora from precursors in plant foods and has been implicated in protection against cancer. We study the effect of enterolactone on the risk of a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested case-control study by linkage of 3 biobanks to the cancer registries in Finland, Norway and Sweden, respectively. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of prostate cancer at a mean follow-up time of 14.2 years after blood collection and among 2,550 control men matched within each cohort for age (+/-2 years), date of blood collection (+/-2 months) and county. The median enterolactone concentrations did not differ between case and control subjects in the full study group (8.4 nmol/L [25th-75th percentile = 4.5-15.0] vs. 8.5 nmol/L [25th-75th percentile = 4.3-15.9]), nor in the national groups. Odds ratios of prostate cancer risk estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles in the full study group were 1.00 (referent), 1.21 (95% confidence interval [CI] = 0.96-1.52), 1.16 (95% CI = 0.91-1.47) and 1.08 (95% CI = 0.83-1.39). The OR estimate for the highest vs. the lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish and Swedish cohort was 1.21 (95% CI = 0.91-1.60), 1.02 (95% CI = 0.59-1.76) and 0.87 (95% CI = 0.45-1.67), respectively. No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found.

Autoimmunity to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk.

Heat shock protein 60 (Hsp60) and Chlamydia pneumoniae infection have both been associated with cardiovascular diseases. Our aim was to study the role of Hsp60 antibodies as coronary risk predictors and their association with C pneumoniae infection and inflammation. This was a prospective, nested, case-control study. The cases consisted of 239 middle-aged Finnish men who developed myocardial infarction or coronary death during the follow-up. Baseline levels of IgA and IgG antibodies to human-specific and C pneumoniae-specific Hsp60 were measured by enzyme immunoassay. Human Hsp60 IgA, but not IgG or C pneumoniae Hsp60, antibodies were a significant risk factor for coronary events (odds ratio 2.0, 95% CI 1.1 to 3.6, when the fourth and first quartiles are compared). When an elevated human Hsp60 IgA antibody level (above the second quartile) was present simultaneously with a high C pneumoniae IgA antibody level (the third quartile) and an elevated C-reactive protein level (the second quartile), compared with all factors at low levels, the risk was 7.0 (95% CI 2.6 to 19.1) without adjustment and 5.0 (95% CI 1.8 to 14.2) when adjustment was made for age and smoking. In conclusion, an elevated human Hsp60 IgA antibody level was a risk factor for coronary events, especially when it was present together with C pneumoniae infection and inflammation.